Relación de IMC con marcadores de inflamación y hemoglobina glicosilada en niños y jóvenes con diabetes mellitus 1 / Relationship of BMI with markers of inflammation and glycosylated hemoglobin in children and young adults with diabetes mellitus 1

La diabetes mellitus tipo 1 (DM1) es una enfermedad autoinmune que genera dependencia exógena de insulina de forma permanente, presenta inflamación subclínica crónica lo que conlleva a una elevación de marcadores de inflamación como factor de necrosis tumoral alfa (TNF-α), proteína C reactiva (PCR) e interleuquina 6 (IL-6). OBJETIVO: determinar la relación entre el IMC sobre los marcadores de inflamación y el control metabólico en niños y jóvenes con DM1 entre 5 a 15 años de edad. METODOLOGÍA: Se realizó un estudio clínico, observacional, exploratorio. A partir de La recolección de datos de fichas clínicas y muestras de sangre en el Instituto de Investigaciones Materno Infantil (IDIMI) del Hospital San Borja Arriarán de la Universidad de Chile. Clasificación del estado nutricional utilizando datos registrados en ficha clínica. Marcadores de inflamación por medio de ELISA, hemoglobina glicosilada mediante métodos estándares. El análisis estadístico incluyó correlaciones mediante test de Spearman y diferencia de medias mediante test de Kruskal-Wallis seguido de post hoc Dunns. RESULTADOS: Un 30% de los pacientes con DM1 presentaron malnutrición por exceso. Al analizar la relación entre los niveles de marcadores inflamatorios y Hb glicosilada se observó la existencia de asociacion positiva entre usPCR y HbA1c (r= 0,30; p=0,0352) y entre IL-6 y HbA1c (r= - 0,038; p=0,0352). CONCLUSIONES: este estudio describe una posible asociación entre parámetros clásicos de inflamación con la hemoglobina glicosilada en las categorias de sobrepeso y obesidad en pacientes con DM1.

Type 1 diabetes mellitus (T1D) is an autoimmune disease that generates permanent exogenous insulin dependence, accompanied by chronic subclinical inflammation that leads to an elevation of inflammation markers such as tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and interleukin-6 (IL-6). OBJECTIVE: To determine the relationship between BMI on markers of inflammation and metabolic control in children and young people with T1D between 5 and 15 years of age. METHODOLOGY: A clinical, observational and exploratory study was carried out, based on the collection of data from clinical records and blood samples of children and adolescents with DM1 at the Instituto de Investigaciones Materno Infantil (IDIMI) of the Hospital San Borja Arriarán of the Universidad de Chile. Nutritional status, levels of inflammation markers and glycosylated hemoglobin were determined by standardized methods. Statistical analysis included correlations by Spearman test and mean difference by Kruskal-Wallis test followed by post hoc Dunns test. RESULTS: A total of 56 patients with T1D were analyzed, 30% of whom presented excess malnutrition. Those children or adolescents with obesity presented significantly higher usPCR levels compared to underweight patients or patients at risk of malnutrition (p=0.039). In addition, HbA1c levels were determined which were negatively associated with usPCR (r= 0.30; p=0.0352) and IL-6 (r= - 0.038; p=0.0352) levels. CONCLUSIONS: This study points out that nutritional status is associated with usPCR levels, in agreement with what is described in the literature and shows a possible association between classical parameters of inflammation with glycosylated hemoglobin in children and adolescents with nutritional diagnosis of overweight or obesity.

Frecuencia de anticuerpos anti-transglutaminasa y antiendomisio en pacientes con diabetes tipo 1 / Association of type 1 diabetes mellitus with celiac disease

Background: Type 1 diabetes mellitus and celiac disease share common genetic and immunological aspects and celiac disease is more common among type 1 diabetic patients. Aim: To determine the frequency of anti endomysial and anti transglutaminase antibodies among patients with type 1 diabetes. Material and Methods: Anti endomysialantibodies determined by indirect immunofluorescence an anti transglutaminase antibodies determined by ELISA were measured in 410 serum samples of patients with type 1 diabetes. Results: Seventy one samples (17 percent) had positive anti transglutaminase antibodies. Among these, 17 had also positive anti endomysial antibodies. In 11 of these 17 patients, the presence of celiac disease was confirmed. Conclusions: Among patients with type 1 diabetes mellitus, the frequency of celiac disease is three times higher than in the general population.

Marcadores de inflamación y autoinmunidad en pacientes con diabetes tipo 1 / And inflammation markers in patients with diabetes autoimmunity type 1

To determine the serological levels of inflammatory markers and autoimmunity in patients with T1D compared with controls, and determined its relation to the duration of diabetes. Methods: We selected 139 patients with T1D without chronic complications of diabetes, and 110 control subjects without family history of diabetes. Serological ultrasensitive C-reactive protein levels (usCRP), interleukin- 6 and adhesion protein VCAM through ELISA assay were determined. Autoimmune profile was also analyzed through GAD65, IA-2 and ZnT8 autoantibodies. Results: Increased levels of usCRP 1.74 (0.10 to 13.6) vs 1.08 (0.40 to 3.70) ng/ml (p < 0.03), VCAM 236.0 (122.2 to 693.5) vs 185.4 (101.3 to 421.3) ng/ml, p < 0.02 and IL-6 1.73 (0.40 to 9.10) vs 1.28 (0.30 to 4.60) ng/ml, p < 0.05 was found in the group of T1D patients compared with the control group. When analyzing inflammatory markers according to age groups (0-10 years and > 10 years), the values of usCRP were higher in the second group. There was no significant association between patients with DM1 and autoimmune positive profile with a higher frequency of markers of inflammation. Conclusions: These results suggest the presence of pro-inflammatory state is considerably more frequent in patients with T1D. The increased level of usCRP and IL -6 and according to age of the patients could indicate a possible role of adiposity and weight gain during the adolescence in the higher frequency of inflammatory markers in T1D patients...

Insulinoma, presentación y evolución de dos casos clínicos / Insulinoma, evolution and presentation of 2 clinical cases

Insulinoma is a very uncommon tumor in children, with an incidence in adults of 2 per million inhabitants. Clinical manifestations include neuroglycopenic or autonomic manifestations due to hypoglycemia. We describe 2 pediatric patients with insulinoma, characterized by repeated episodes of hypoglycemia associated to high insulin serum levels and presence of a small mass in the pancreas by imaging studies. The diagnosis was very prompt in one case and delayed in the other, emphasizing the need for an appropriate diagnosis of hypoglycemia during childhood.

El insulinoma es un tumor muy infrecuente en la edad pediátrica y la incidencia reportada en adultos es de 2 casos por millón de habitantes. La presentación de la enfermedad consiste en la presencia de síntomas neuroglicopénicos y autonómicos desencadenados por los episodios de hipoglicemia. Se describen dos pacientes con insulinoma esporádico. El cuadro clínico consistió en episodios repetidos de hipoglicemia asociados a niveles aumentados de insulina sérica y a imágenes sugerentes de un tumor pancreático. El diagnóstico fue muy oportuno en uno de los casos y muy tardío en el otro, lo que resalta la necesidad de estar muy alerta ante casos de hipoglicemia durante la niñez.

[Fasting glucose versus oral glucose tolerance test for detection of glucose intolerance in obese children]. / Glicemia de ayuno versus prueba de tolerancia oral a la glucosa en la detección de intolerancia a la glucosa en niños y adolescentes obesos.

BACKGROUND: Recently, the cut-off point for normal fasting glucose (FG) level, was decreased to 100 mg/dl. AIM: To determine the frequency of abnormal carbohydrate abnormalities in children with obesity and evaluate if the fasting glucose level is a useful tool for the screening of glucose intolerance (GI). PATIENTS AND METHODS: Children and adolescents, referred for evaluation of obesity were evaluated with an oral glucose tolerance test (OGTT) and FG. The sensitivity of FG for detection of GI, using the 100 and 110 mg/dl cut-off point, was evaluated. RESULTS: We studied 186 patients (125 females) aged 12.1 (range: 5.4-19.3) years with a body mass index (BMI) of 29.9 (18.3-44.6) kg/mt2 and a BMI Z score of 2.1 (1.7-3.2). Seven patients (3.8%) had abnormalities in the carbohydrate metabolism. The sensitivity of FG for the detection of GI using the 100 and 110 mg/dl cut-off values was 42.9 and 14.3%, respectively. Receiver operating characteristic (ROC) curves showed that the optimal diagnostic level for FG corresponds to 80 mg/dl (sensitivity: 85.7% and specificity of 74.9%). CONCLUSIONS: An abnormal carbohydrate metabolism was detected in 3.8% of the obese children and adolescents in this sample. FG of 100 mg/dl does not detect 57.1% of the patients with glucose intolerance. These data suggest that FG is not a useful screening tool for glucose intolerance in young patients.

Glicemia de ayuno versus prueba de tolerancia oral a la glucosa en la detección de intolerancia a la glucosa en niños y adolescentes obesos / Fasting glucose versus oral glucose tolerance test for detection of glucose intolerance in obese children

Background: Recently, the cut-off point for normal fasting glucose (FG) level, was decreased to 100 mg/dl. Aim: To determine the frequency of abnormal carbohydrate abnormalities in children with obesity and evaluate if the fasting glucose level is a useful tool for the screening of glucose intolerance (GI). Patients and methods: Children and adolescents, referred for evaluation of obesity were evaluated with an oral glucose tolerance test (OGTT) and FG. The sensitivity of FG for detection of GI, using the 100 and 110 mg/dl cut-off point, was evaluated. Results: We studied 186 patients (125 females) aged 12.1 (range: 5.4-19.3) years with a body mass index (BMI) of 29.9 (18.3-44.6) kg/mt² and a BMI Z score of 2.1 (1.7-3.2). Seven patients (3.8 percent) had abnormalities in the carbohydrate metabolism. The sensitivity of FG for the detection of GI using the 100 and 110 mg/dl cut-off values was 42.9 and 14.3 percent, respectively. Receiver operating characteristic (ROC) curves showed that the optimal diagnostic level for FG corresponds to 80 mg/dl (sensitivity: 85.7 percent and specificity of 74.9 percent). Conclusions: An abnormal carbohydrate metabolism was detected in 3.8 percent of the obese children and adolescents in this sample. FG of 100 mg/dl does not detect 57.1 percent of the patients with glucose intolerance. These data suggest that FG is not a useful screening tool for glucose intolerance in young patients.

Diabetes Mellitus tipo 1 (DM1) en niños menores de 5 años: Características al debut vs otros grupos etarios en Chile / Type I diabetes mellitus in Chilean children under 5 years-old: Onset characteristics in contrast with other age groups

Introducción: En los últimos años, se ha visto un aumento en la incidencia de DM1 en niños. Objetivo: Determinar frecuencia y características clínicas y de laboratorio al debut de DM1 en niños chilenos menores de 5 años, comparado con los de mayor edad. Pacientes y Métodos: Se estudiaron los datos clínicos y de laboratorio de pacientes que debutaron entre 1998-2003 en cuatro centros de Santiago. Se clasificaron en 3 grupos etarios (G): 0-4 (GI), 5-9 (GII) y 10-14 años (GIII) y se compararon según los parámetros descritos. Resultados: Un 19,7 por ciento de los pacientes eran menores de 5 años; GI (n = 27), seguido de aquéllos pertenecientes a GII (43,8 por ciento; n = 60) y GIII (36,5 por ciento; n = 50). El periodo de síntomas previo al diagnóstico fue más corto en GI; 18,4 ± 23,7 vs 26,4 ± 27,4 y 40,1 ± 60 días (p < 0,0001) y su nivel de HbA1c fue más baja; 10,1 ± 1,7 vs 11,8 ± 3,4 por ciento en GII (p < 0,0001) y 12,4 ± 2,6 por ciento en GIII (p = 0,028), respectivamente. No hubo diferencias en la glicemia inicial entre los grupos. La acidosis metabólica fue mayor en GI; pH 7,14 ± 0,1 vs 7,19 ± 0,2 (GII) y 7,26 ± 0,1 (GIII) (p < 0,0001) y presentaron más infecciones concomitantes (33 por ciento, 20 y 28 por ciento respectivamente; p > 0,05). Conclusiones: Un porcentaje importante de las DM1 se inicia en niños < 5 años. Este grupo presenta un cuadro más grave, con mayor acidosis, menores niveles de HbA1c y periodo previo de síntomas, por lo que debe existir alerta para el diagnóstico en este grupo etario.

Background: During the last years, an increase in the incidence of DM1 in infants has been observed. Objective: to study the number of children younger than 5 years-old diagnosed with DM1 and compare clinical and laboratory features with older children at DM1 onset. Method: Study of the clinical and laboratory characteristics in subjects diagnosed with DM1 from 1998 to 2003 in Santiago. Patients were classified according to age in 3 groups: 0-4 (GI), 5-9 (GII) and 10-14 years-old (GIII). Results: 19,7 percent cases were younger than 5 years-old (GI n = 27), GII (43,8 percent n = 60) and GIII (36,5 percent n = 50). A shorter duration of symptoms was observed in GI (18,4 ± 23,7 vs 26,4 ± 27,4) (p < 0,0001) and HbA1c levels were lower in GII (10,1 ± 1,7 vs 11,8 ± 3,4 percent) (p < 0,0001) and in GIII (12,4 ± 2,6 percent) (p = 0,028). Glucose levels were similar among groups (p>0,05) and metabolic acidosis was more severe in GI (pH 7,14 ± 0,1 vs 7,19 ± 0,2 in GII and 7,26 ± 0,1 in GIII) (p < 0,0001). A concomitant infectious disease was observed in GI (33 percent), GII (20 percent) and GIII (28 percent) (p > 0,05). Conclusions: An important percentage of DM1 in children presents in subjects younger than 5 years-old. This group showed acute and severe clinical presentation with longer duration of symptoms, severe acidosis and lower HbA1c levels. It is necessary to evaluate carefully in order to suspect the diagnosis in this group.

[IGF-I sensitivity in small for gestational age children]. / Sensibilidad a IGF-I en niños pequeños para la edad gestacional.

BACKGROUND: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). AIM: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). PATIENTS AND METHODS: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine). RESULTS: At the time of the study, the Z scores for height among children with and without CUG were -1.55 +/- 0.22 and -3.24 +/- 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 +/- 0.5 and 5.6 +/- 0.6 ng/ml, respectively). After Somatokine administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine. CONCLUSIONS: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG.

Sensibilidad a IGF-I en niños pequeños para la edad gestacional / IGF-I sensitivity in small for gestational age children

Background: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). Aim: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). Patients and methods: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine®). Results: At the time of the study, the Z scores for height among children with and without CUG were -1.55 ± 0.22 and -3.24 ± 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 ± 0.5 and 5.6 ± 0.6 ng/ml, respectively). After Somatokine® administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine® administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine®. Conclusions: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG.

Nuevos esquemas de tratamiento con insulina en niños y dolescentes con Diabetes Mellitus tipo 1 (DM1) en un Hospital Público / New schemes of insulin treatment in children and adolescents with type 1 diabetes mellitus attending a Public Hospital

En la última década se ha demostrado la importancia del control glicémico en la prevención de las complicaciones microvasculares de la DM1. Para lograr este objetivo se ha propiciado el uso de esquemas terapéuticos de insulina intensificados. Objetivo: Comunicar los nuevos esquemas terapéuticos que se utilizan en niños y adolescentes con DM1 y sus resultados en el control metabólico. Método: Se evaluaron los esquemas insulínicos utilizados por todos los pacientes < 19 años en control durante 2003, clasificándolos en tratamiento intensificado (doble o triple dosis de NPH o Glargina) o convencional (< 2 dosis/día). Se consignaron las dosis utilizadas, la HbA1c promedio, el resultado del programa educativo (conocimiento de cantidad de hidratos de carbono, intercambio de alimentos, cambio de dosis según ingesta de hidratos de carbono (HdC) y proporción Insulina/ HdC) y se compararon los resultados obtenidos con las distintas modalidades de tratamiento. Resultados: Se estudiaron 69 pacientes con DM1 (36 mujeres), de 12,0 ± 3,7 años (2-19 años), 59,7% púberes. Todos utilizaban una insulina basal (69,2% de la dosis diaria) y otra prandial; 87% de los pacientes requirieron tres o más dosis diarias de insulina y 13% utilizaba esquema convencional de dos dosis de NPH. Los pacientes en tratamiento intensificado recibían tres o cuatro dosis diarias de insulina prandial, con los siguientes esquemas de insulina basal: dos dosis diarias de NPH (28%), glargina (10%) y tres dosis diarias de NPH (49%). 88,4% de los pacientes modificaba la dosis de insulina rápida según la glicemia y 46,4% consideraba la ingesta de HC; 27% conocía la relación HdC/insulina y 79,7% se colocaba refuerzos adicionales de insulina al comer fuera de sus horarios. La HbA1C del grupo fue de 8,6 ± 1,4%; 30,4% de los pacientes logró el objetivo de HbA1c establecido en el programa, sin diferencias respecto al esquema de insulinoterapia basal utilizado. Por análisis de ...

Introduction: During the last decade the importance of glycaemic control in the prevention of microvascular complications of type 1 diabetes mellitus (DM1) has been demostrated. To achieve this goal, different modalities of intensive therapy have been recommended. Objective: To communicate a novel therapeutic modality employed in paedriatric patients and the metabolic control achieved. Methods: All DM patients < 19 years were included. Insulin treatment was consigned and classified as intensive (at least 3 daily doses, 2 or 3 NPH daily doses, or glargin) or conventional (2 or less doses). Number of doses, mean HbA1c during 2003, results of educative programmes were evaluated and compared. Results: 69 patients (36 females) were studied, 59,7% were pubertal, with a mean age of 12,0 ± 3,7 years. All patients used a basal insulin (69,2% daily dose) and a prandial insulin. Intensive therapy was used by 87% of children. Patients with multiple daily doses received 3 or 4 inyections of a short or rapid acting insulin. Basal insulin was glargine in 10%, twice daily NPH in 28% and thrice daily in 49%. Patients modified dose according to glucose level occured in 88,4%, and 46,4% considered carbohydrate intake. 27% knew the carbohydrate/insulin ratio and 79,7% used additional insulin when eating extra carbohydrates. The BbA1c was 8,6 ± 1,4% without differences in terms of insulin modality used. 30,4% achieved the proposed goals of HbA1c. The total and basal insulin usage correlated with the HbA1c. Conclusions: Multiple modalities of insulin therapy are available, no difference in metabolic control between the modalities was detected. We have achieved very good control in 30% of the patients, only insulin daily dose and basal dose correlated significatively with HbA1c.

Cronología del desarrollo puberal en niñas escolares de Santiago: relación con nivel socio-económico e índice de masa corporal / Age of pubertal events in Chilean school age girls and its relationship with socioeconomic status and body mass index

Background: Recent studies in the United States have demonstrated that a significant proportion of girls show thelarche before the age of eight years. Nutritional status, geographic influences and racial factors are known to affect the timing of puberty. Aim: To evaluate the age of onset of puberty, development of secondary sexual characteristics and menarche in Chilean girls, and its relation to obesity and socioeconomic status. Material and methods: Healthy girls attending elementary school, from first to ninth grade in Santiago, Chile, were studied. A pediatric endocrinologist evaluated pubertal development using Tanner classification. Breast development was assessed by inspection and breast palpation. Average age of onset of pubertal events was determined by probit analysis. Results: A total of 758 girls, aged 5.8 to 16.1 years, were recruited. Obesity, defined as a BMI greater than 90th percentile, was found in 24.4 percent. The age of menarche was 12.7 years, the onset of Tanner stage 2 breast development and pubic hair was at 8.9 and 10.4 years, respectively. Sixteen percent of girls aged 7 to 7,9 years, had thelarche. Upper class girls showed a later onset of breast Tanner stage 4 stage than low-middle class girls. Obesity was not found in logistic regression analysis to be a significant predictive factor in the onset of puberty. Conclusions: The age of menarche has not changed in the last thirty years, but an earlier onset of thelarche has occurred. The high frequency of thelarche between 7 and 8 years suggests that the normal age of breast development should be revised.

Cambios en la edad de inicio de la pubertad en niñas de la comuna de Santiago: implicancias para el diagnóstico de la pubertad precoz / Changes in the age of puberty in girls at Santiago: implications for the diagnosis of precocious puberty

Introducción: Existe evidencia en la literatura norteamericana que la edad de inicio de la pubertad en las niñas se estaría adelantando. No existen trabajos que prmitan establecer este hecho en nuestra población. Objetivo: Evaluar la edad de inicio de desarrollo puberal en niños y niñas que asisten a 3 colegios del cector céntrico de Santiago. Sujetos y métodos: Se reclutaron 332 niños , se determinó peso, talla e IMC (peso/talla) y se descartaron los 80 (24 por ciento) con IMC < p10 o > p95, ingresando 252 escolares (131 niñas). Se realizó examen físico y se consideró como inicio de desarrollo puberal la aparición del tejido mamario en las niñas y un volumen testicular de 4 cc o mayor en los varones. Resultados: En el intervalo de edad de7 a 7.49 años habían 2/20 (10 por ciento) niñas con boton mamario, en el de 7.5 a 7.99 4/16 (25 por ciento) y en el de 8 a 8.99 años 9/36 (25 por ciento). En el varón, el primer signo de activación del eje pituitario gonadal aparecio en el grupo de 9 a 9.49 años, similar a lo descrito previamente. Conclusión: La edad de inicio del desarrollo puberal en este grupo de niñas chilenas, se estaría adelantando en relación a la litaratura clásica, mientras que en el varó no se demuestran cambios. Estos resultados sugieren que el inicio del desarrollo mamario en las niñas entre los 7 y 8 años, no debería considerarse siempre como patológico y que habría que reevaluar la definició de pubertad precoz

Utilidad de la determinación del factor de crecimiento insulino-simil tipo I (IGF-I) y de su proteína ligante tipo 3 (IGFBP-3) en el diagnóstico de la deficiencia de hormona de crecimiento en niños / Usefulness of the measurement of insulin-like growth factor 1 (IGF-I) and IGF-1 binding protein-3 (IGFBP-3) for the diagnosis of growth hormone (GH) deficiency in children

Background: The diagnosis of GH deficiency (GHD) is based upon the results of GH stimulation tests, which have several drawbacks. Aim: To evaluate the usefulness of IGF-1 and IGFBP-3 for the diagnosis of GHD in prepuberal children. Material and methods: We measured IGF-I and IGFBP-3 in three group of subjects: I. GHD (n:24), height <-2SD for age (Z score, average ñ SD: -4.2 ñ 1.2), growth velocity 7 ng/ml (15.3 ñ 6.9 ng/ml), y III. Normal school children (n:35) with normal heights (-0.17 ñ 0.12 SD) were studied as controls. Results: IGF-1 and IGFBP-3 were significantly lower in GHD than in NGHD and controls (p <0.001), and in NGHD than in C (p <0.001). We defined the normal range of both proteins as ñ 2 SD of the mean of the control group. Using this criteria, IGF-I was low in 21/24 GHD, and in 12/32 NGHD. IGFBP-3 was low in 22/24 GHD, and in 6/32 NGHD. Only 1 GHD patient had both exams in the normal range, suggesting that he is probably NGHD. 4/32 of the NGHD had both exams below normal range, suggesting that they are probably GHD. Conclusions: IGF-1 and IGFBP-3 are important tools for the diagnosis of GHD

Respuesta al factor liberador en niños con deficiencia de hormona de crecimiento / Growth hormone response to releasing factor in growth hormone deficient children

El factor liberador de hormona de crecimiento (GRF) es un péptido de 44 aminoácidos producido en el hipotálamo, que estimula la secreción de hormona de crecimiento (GH) por la hipófisis. Este factor fue administrado a 21 niños prepuberales (12 varones y 9 mujeres) portadores de deficiencia de hormona de crecimiento. La edad cronológica promedio fue de 8,9 ñ 3,5 años, y su edad ósea de 5,6 ñ 2,6 años. El diagnóstico de deficiencia de GH se basó en una talla 2 DE bajo la media, velocidad de crecimiento inferior a 4,5 cm/año, respuesta inferior a 7 ng/ml a 2 diferentes pruebas de estímulo para GH, y ausencia de otras afecciones. La respuesta al estímulo con GRF fue definida como positiva cuando los niveles de GH aumentaron por sobre 4 veces al coeficiente de variación del radioinmunoensayo utilizado, lo que se registró en 13 de los 21 pacientes (62%). La respuesta máxima al GRF fue 17,2 ñ 10,8 ng/ml y se observó entre 5 y 30 min después de su administración. Los resultados positivos en 62% de los pacientes estudiados sugieren que sus defectos residen en el hipotálmo más que en la hipófisis. Estos niños se podrían beneficiar de un tratamiento a largo plazo con GRF